This grant allows participation in the RTOG Cooperative Trials for Phase I, II and III studies. Participation in Phase I and II studies has been involved with radiation sensitizers and hyperthermia. Clinical participation in Phase III protocols will concentrate on curable rather than metastatic protocols. We will continue to be the major contributor to the prostate protocols. The hyperthermia studies have required development of microwave generators, applicators and methods of thermal measurement. Roswell Park Memorial Institute is one of the leading research institutes in the development of microwave applicators. A complete new generation of microwave applicators has recently been designed and are being tested in conjunction with the Bureau of Radiological Health. Development work has been started on a 13.5 MHz induction system for heating deep tumors. Clinical trials will incorporate aspiration cytology performed through deep tumor of temperature cannula. The C3H mouse has been developed as a small animal system to study the neurotoxicity of nitroimidazoles. Employing both behavioral tests and histological studies, the relative neurotoxicities of different radiosensitizers are being compared and the mechanisms via which these compounds produce central and peripheral nervous system damage is being investigated. Information gained will be applicable to patients in RTOG protocols. Roswell park will participate in the Phase I study of desmethylmisonidazole. The development work in hyperthermia in the past and current and much of the other work outlined here is supported by RTOG funds only.